rs4933977

Positions:

• chr10-84205818-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033100.4(CDHR1):​c.863-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,609,556 control chromosomes in the GnomAD database, including 3,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (907 hom., cov: 32)
  • Exomes 𝑓: 0.046 (2981 hom.)
• Consequence: CDHR1 NM_033100.4 intron
• Scores: Splicing: ADA: 0.00002035
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.27

Genes affected

CDHR1 (HGNC:14550): (cadherin related family member 1) This gene belongs to the cadherin superfamily of calcium-dependent cell adhesion molecules. The encoded protein is a photoreceptor-specific cadherin that plays a role in outer segment disc morphogenesis. Mutations in this gene are associated with inherited retinal dystrophies. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-84205818-C-T is Benign according to our data. Variant chr10-84205818-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR1	NM_033100.4	c.863-9C>T		intron_variant		ENST00000623527.4	NP_149091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4	c.863-9C>T		intron_variant		1	NM_033100.4	ENSP00000485478.1
CDHR1	ENST00000332904.7	c.863-9C>T		intron_variant		1		ENSP00000331063.3
CDHR1	ENST00000372117.6	c.242-9C>T		intron_variant		2		ENSP00000361189.4
CDHR1	ENST00000624091.1	n.139C>T		non_coding_transcript_exon_variant	2/4	5		ENSP00000485460.1

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12972 AN: 152096 Hom.: 907 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0942

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0738

GnomAD3 exomes AF: 0.0758 AC: 18935 AN: 249874 Hom.: 1244 AF XY: 0.0703 AC XY: 9503 AN XY: 135132

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.0326

Gnomad EAS exome AF: 0.184

Gnomad SAS exome AF: 0.0851

Gnomad FIN exome AF: 0.0193

Gnomad NFE exome AF: 0.0298

Gnomad OTH exome AF: 0.0556

GnomAD4 exome AF: 0.0462 AC: 67324 AN: 1457342 Hom.: 2981 Cov.: 30 AF XY: 0.0468 AC XY: 33967 AN XY: 725182

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.0341

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.0894

Gnomad4 FIN exome AF: 0.0198

Gnomad4 NFE exome AF: 0.0304

Gnomad4 OTH exome AF: 0.0564

GnomAD4 genome AF: 0.0853 AC: 12991 AN: 152214 Hom.: 907 Cov.: 32 AF XY: 0.0860 AC XY: 6399 AN XY: 74418

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0929

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.0769

Alfa AF: 0.0453 Hom.: 364

Bravo AF: 0.0970

Asia WGS AF: 0.138 AC: 477 AN: 3478

EpiCase AF: 0.0306

EpiControl AF: 0.0325

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Cone-Rod Dystrophy, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.6
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4933977; hg19: chr10-85965574; COSMIC: COSV60564886; COSMIC: COSV60564886;